WO 97/45401, incorporated by reference herein, discloses guanidine derivatives of the general formula (1)
in which X represents the group, —R1, —NHR1, —NH—NH—CHR1R2 or —NH—N═CR1R2, whereby R1 and R2 independent of each other represent hydrogen, a linear or branched C3–C20 alkyl or C3–C20 cycloalkyl, adamantyl, norbornyl, tricyclodecyl or benzyl, pyridyl, indolyl, quinolyl, anthracyl, phenantryl, perinaphthyl or quinuclidinyl radical. The use of the compounds as active ingredient in pharmaceutical preparations is based mainly on the inhibition of sphingomyelinases. The free bases are described exclusively as examples of compounds according to formula 1.
Due to their detergent structure, the bases described and their salts obtained by neutralization with inorganic acids or by dissolution in buffered saline (physiological sodium chloride solution) possess strong hemolytic and tissue-damaging properties. Moreover, in the presence of inorganic phosphate ions, inorganic salts form phosphates of the guanidines which are insoluble in aqueous solutions. This causes them to be precipitated, and thereby rendered pharmaceutically inactive, in the blood at relatively low concentrations. For these reasons, the pharmaceutical utility of guanidine derivatives is strongly limited.